Heparin-Brij S10 conjugate micelle system enhances the anticancer efficacy of celecoxib against breast cancer cells

Celecoxib (CXB), a COX-2-selective nonsteroidal anti-inflammatory drug, exhibits promising anticancer activity but suffers from poor aqueous solubility and low bioavailability. In this study, a heparin-Brij S10 amphiphilic conjugate (Hep-Brij) was synthesized <i>via</i> cystamine linkage to develop self-assembled micelles for enhanced CXB delivery. The Hep-Brij micelles displayed a uniform nanoscale size (116.8 nm), negative surface charge (-26.3 mV), and high encapsulation efficiency (99.07%) with a drug loading of 4.71%. The micellar system demonstrated pH-responsive release, showing faster CXB liberation at physiological pH (7.4) and slower release under acidic conditions (pH 5.0), indicating potential for controlled and site-specific drug delivery. Hemocompatibility and cytocompatibility assays confirmed excellent biocompatibility below 200 µg/mL. Remarkably, CXB-loaded Hep-Brij micelles achieved a 59.3-fold lower IC₅₀ value (0.89 ± 0.07 µg/mL) against MCF-7 breast cancer cells compared to free CXB (52.78 ± 1.26 µg/mL), underscoring enhanced intracellular uptake and cytotoxicity. The synergistic contributions of heparin and Brij S10 underpin the superior therapeutic outcome. These results demonstrate that Hep-Brij micelles represent a safe and potent nanoplatform for improving CXB delivery and efficacy in breast cancer therapy.